Gene Regulation results in differential Gene Expression, leading to cell Specialization

1. Gene Regulation results in differential Gene Expression, leading to cell Specialization Eukaryotic DNA

2. Epigenetics – Ghost in Your Genes • Watch to see how your environment and your choices influence inheritance… • http://www.youtube.com/watch?v=CiAyLPeCTMU&feature=share&list=PLA2E1F3FFBFAE1CB6

3. Differential Gene Expression • Nucleosome Packing: DNA wraps around histone proteins to form a structure called a nucleosome. Nucleosomes help pack DNA into eukaryotic chromosomes. • When acetyl groups attach to the histone proteins the DNA in chromosomes loosens to allow for transcription. • The addition of methyl groups to histone proteins can cause DNA to condense thus preventing transcription. • In Genomic Imprinting, methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of development.

4. Fig. 18-8-3 Organization of Typical Eukaryotic Genes Poly-A signal sequence Enhancer (distal control elements) Proximal control elements Termination region Exon Intron Exon Intron Exon DNA Upstream Downstream Promoter Transcription Exon Intron Exon Intron Exon Primary RNA transcript Cleaved 3 end of primary transcript 5 RNA processing Intron RNA Poly-A signal Coding segment mRNA 3 Start codon Stop codon Poly-A tail 3 UTR 5 Cap 5 UTR

5. The Roles of Transcription Factors • Regulatory Proteins, repressors and activators, operate similarly to those in prokaryotes, influencing how readily RNA polymerase will attach to a promoter region. In many cases, numerous activators are acting in concert to influence transcription.

6. Fig. 18-9-3 Promoter Activators Gene DNA Distal control element Enhancer TATA box General transcription factors DNA-bending protein Group of mediator proteins RNA polymerase II RNA polymerase II Transcription initiation complex RNA synthesis

7. Coordinately controlled eukaryotic genes • A particular combination of control elements can activate transcription only when the appropriate activator proteins are present. • All cells of an organism have all chromosomes/genes but certain genes are only active in certain cells. The transcription factors present in the cell determine which genes will be active and which won’t (but they are both still present)

8. Fig. 18-10 Enhancer Promoter Albumin gene Control elements Crystallin gene LIVER CELL NUCLEUS LENS CELL NUCLEUS Available activators Available activators Albumin gene not expressed Albumin gene expressed Crystallin gene not expressed Crystallin gene expressed (a) Liver cell (b) Lens cell

9. Post Transcriptional Regulation • Alternate Gene Splicing - different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns

10. Fig. 18-11 Exons DNA Troponin T gene Primary RNA transcript RNA splicing or mRNA

11. Noncoding RNAs role in gene expression • RNA Interference, noncoding RNAs play multiple roles in controlling gene expression. MicroRNAs (miRNAs) and Small inserting RNAs (siRNAs) are small single-stranded RNA molecules that can bind to mRNA. These can degrade mRNA or block its translation. The difference between the two is that they form from different RNA precursors.

12. Fig. 18-13 Hairpin miRNA Hydrogen bond Dicer miRNA miRNA- protein complex 5 3 (a) Primary miRNA transcript mRNA degraded Translation blocked (b) Generation and function of miRNAs